The innovation engine for new materials

Zina Helal

Zina Helal

Major: 

Biomedical Engineering

University: 

University of Texas at San Antonio

Mentor(s): 

Sarah Innes Gold

Faculty Sponsor(s): 

Omar Saleh

Faculty Sponsor's Department(s): 

Materials

Project Title: 

Complexes of aggrecan and hyaluronic acid determine structural and mechanical properties of soft tissue

Project Description: 

Aggrecan proteins bind to hyaluronic acid (HA) polymers in articular cartilage, forming a molecular complex responsible for resisting compressive loads. Aggrecan has a large, charged structure comprised of a protein core with many sugar side chains. This molecule is important because it attracts water, creating a stiff, swollen matrix. Its breakdown is associated with degenerative bone disease such as osteoarthritis. It is still unclear how changes in concentration of available binding aggrecan affect the size and structure of HA complexes which in turn influence the structural response of tissue to external forces. While there are intricate cellular mechanisms influencing in vivo mechanics, assembling these complexes in vitro allows us to precisely study how concentrations of aggrecan affects the structure of HA polymers. Here, we quantify the extension of single HA polymers in solutions containing aggrecan concentrations between 0 mg/ml – 2 mg/ml. This study was conducted with magnetic tweezers, a microscopic method that applies controlled force to a single polymer chain and measures the associated extension. This technique is advantageous as it allows for measuring the mechanical response of the same molecule in different solutions. From these measurements, we generate force-extension curves that show how polymer structure varies with aggrecan concentration. As aggrecan binds more densely, the complex swells as indicated by a larger measured extension. It is expected that a larger extension translates to healthier increased tissue stiffness in vivo. We found individual HA polymers demonstrated an increase in extension up to an aggrecan solution concentration of 1 mg/ml, above which additional aggrecan did not increase HA extension, suggesting saturation. Our results show how insufficient amounts of aggrecan weaken the microscopic components of cartilage that are vital to healthy tissue function.